(1) We have previously used the N-terminal fusion peptide of the gp41 envelope glycoprotein from human immunodeficiency virus type 1 (HIV-1) as a mechanistic probe to identify chemokine receptors as the point of viral entry into target cells. We now have performed experiments showing that the gp41 fusion peptide can use various types of chemokine receptors (i.e. CXCR4, STRL33, STRL22, CCR5, and CCR2B) to enter different animal cells [i.e. HeLa, WI-38 (human lung), HOS (human bone cancer), HK 293 (human kidney), Jurkat, and Molt-3 (immortalized T-cell), Vero (monkey kidney), and mink lung cells]. STRL33 has been reported to serve as the fusion co-receptor for both HIV and its simian counterpart (SIV). Using the fusion peptide of SIV gp41, we confirmed that it could penetrate STRL33-expressing cells. We concluded that most chemokine receptors are gp41 receptors; the selection of a particular chemokine receptor is determined by HIV gp120 after interacting with cellular CD4 interaction. Since each gp41 likely binds to one receptor, the currently popular model of a pre-formed, "spring-loaded" trimeric gp41 complex may be incorrect. Our finding suggests that blocking the point of entry by HIV may be the method of choice to combat HIV infection. (2) A novel magnesium-dependent, calcium-inhibitable type 2C protein phosphatase (MCPP) has been shown by us to co-purify with a leukemogenic protein SET. SET has been reported to potently inhibit type 2A protein phosphatases (PP2A) and to bind tightly to cyclin B. Thus, SET may play an important role in cellular regulation. We have examined SET as an inhibitor of PP2A using several substrates and found only weak inhibition. Similar results were obtained in other laboratories. We concluded that either SET is not a strong inhibitor of PP2A or its inhibitory effect is highly substrate dependent. (3) In collaboration with Dr. Diane Newton and Dr. Susanna Rybak of NCI, the kinetic parameters of a genetically modified Onconase, a cytotoxic ribonuclease (RNase) with anti-tumor properties, has been determined. The mode of inhibition of Onconase by an intracellular RNase inhibitor, PRI, is due to "enzyme depletion". In this mechanism, although the inhibitor binds to the substrate site, the inhibition cannot be relieved by high levels of substrate because of the extremely tight binding of the inhibitor. The resultant inhibition pattern appears identical to the simple non-competitive case since the inhibitor simply reduces the amount of enzyme in the reaction, giving rise only to a reduced maximum velocity.